[Obesity and Eating Disorders. Indications for the different levels of care. An Italian Expert Consensus Document]. / Documento di Consensus. Obesità e Disturbi dell'Alimentazione Indicazioni per i diversi livelli di trattamento.

This paper is an Italian Expert Consensus Document on multidimensional treatment of obesity and eating disorders. The Document is based on a wide survey of expert opinion. It presents, in particular, considerations regarding how clinicians go about choosing the most appropriate site of treatment for a given patient suffering from obesity and/or eating disorders: outpatient, partial hospitalization, residential rehabilitation centre, inpatient hospitalization. In a majority of instances obesity and eating disorders are long-term diseases and require a multiprofessional team-approach. In determining an initial level of care or a change to a different level of care, it is essential to consider together the overall physical condition, medical complications, disabilities, psychiatric comorbidity, psychology, behaviour, family, social resources, environment, and available services. We first created a review manuscript, a skeleton algorithm and two rating scales, based on the published guidelines and the existing research literature. As the second point we highlighted a number of clinical questions that had to be addressed in the specific context of our National Health Service and available specialized care units. Then we submitted eleven progressive revisions of the Document to the experts up to the final synthesis that was approved by the group. Of course, from point to point, some of the individual experts would differ with the consensus view. The document can be viewed as an expert consultation and the clinical judgement must always be tailored to the particular needs of each clinical situation. We will continue to revise the Document periodically based on new research information and on reassessment of expert opinion to keep it up-to-date. The Document was not financially sponsored.

Are behavioural approaches feasible and effective in the treatment of type 2 diabetes? A propensity score analysis vs. prescriptive diet.

BACKGROUND AND AIMS: Lifestyle changes are considered first line treatment in type 2 diabetes, but very few data are available in the "real world" of diabetes units. We aimed to measure the effectiveness of moderate and high intensity interventions on weight loss, metabolic control and insulin use. We report a prospective cohort study, carried out in 822 consecutive subjects with type 2 diabetes, first seen in a 4-year period in a diabetes unit of an academy hospital. METHODS AND RESULTS: Subjects were treated with either a sole prescriptive diet (Diet), or received an additional short-course Elementary Nutritional Education (4 group sessions-ENE) or an intensive Cognitive Behavioural Therapy (12-15 group sessions-CBT). The results were adjusted for the propensity score to be assigned different treatments, derived from logistic regression on the basis of age, gender, BMI, HbA1c, diabetes duration and insulin use at baseline. Main outcome measures were weight loss and weight loss maintenance, metabolic control, and secondary failure to insulin use. Both structured programmes produced a larger weight loss, and the adjusted probability of achieving the 7% weight loss target was increased. Similarly, both programmes favoured metabolic control, irrespective of insulin use. After adjustment for propensity score, both ENE (hazard ratio, 0.48; 95% CI, 0.27-0.84) and CBT (hazard ratio, 0.36; 95% CI, 0.16-0.83) were associated with a reduced risk of de novo insulin treatment. CONCLUSION: Structured behavioural programmes aimed at lifestyle changes are feasible and effective in the "real world" setting of a diabetes unit for the treatment of type 2 diabetes.

Metabolic syndrome, psychological status and quality of life in obesity: the QUOVADIS Study.

OBJECTIVE: We aimed to investigate the association of the clinical variables of the metabolic syndrome (MS) and psychological parameters on health-related quality of life (HRQL) in obesity. In particular, our aim was to investigate the relative impact of physical symptoms, somatic diseases and psychological distress on both the physical and the mental domains of HRQL. DESIGN: Cross-sectional study. SUBJECTS: A cohort of 1822 obese outpatients seeking treatment in medical centers. MEASUREMENTS: HRQL was measured by the standardized summary scores for physical (PCS) and mental (MCS) components of the Short Form 36 Health Survey (SF-36). Patients were grouped according to tertiles of PCS and MCS. Metabolic and psychological profiles of PCS and MCS tertiles were compared by discriminant analysis. RESULTS: The profile of metabolic and psychological variables was tertile-specific in 62.4 and 68.3% of patients in the lowest and highest tertiles of PCS, respectively, while concordance was low in the mid-tertile (32.8%). Concordance was very high in the lowest (74.4%) and in the highest (75.5%) tertiles of MCS, and was fair in the mid-tertile (53.2%). The main correlates of PCS were obesity-specific and general psychological well-being, BMI, body uneasiness, binge eating, gender and psychiatric distress. Only hypertension and hyperglycemia qualified as correlates among the components of MS. The components of MS did not define MCS. CONCLUSIONS: Psychological well-being is the most important correlate of HRQL in obesity, both in the physical and in the mental domains, whereas the features of MS correlate only to some extent with the physical domain of HRQL.

An empowerment-based educational program improves psychological well-being and health-related quality of life in Type 1 diabetes.

Educational programs are reported to improve metabolic control and well-being in Type 1 diabetes mellitus (DM), but the effects of newly- structured interventions, aimed at promoting empowerment in educated patients in active selfcare, have received little attention. Ninety patients with Type 1 DM in intensive insulin treatment were invited to an empowerment-based educational intervention. Changes in quality of life and psychological well-being in the 54 patients participating in the program (median age, 44 yr) were compared with those measured in patients who refused. The following questionnaires were administered at baseline and 12 months later: Psychological General Well-Being (PGWB), Medical Outcome Survey Short-Form 36 (SF-36), and Well-Being Enquiry for Diabetics (WED). Baseline values were indicative of moderate, but significant, psychological distress in the whole cohort. At follow-up, the experimental group had a better metabolic control {glycosylated hemoglobin, -0.4% [time x treatment analysis of variance (ANOVA), p = 0.005 vs controls]}, and a general improvement in comprehensive indices and most scales of PGWB and SF-36. Vitality (p = 0.042) and Social Functioning (p = 0.039) were no longer different from population norm. Similarly, the Symptoms (p = 0.005), Discomfort (p = 0.043) and Impact scales (p = 0.032) of WED, reflecting physical functioning, diabetes-related worries and familial relationships, role functioning and social network, improved significantly in treated patients. An educational empowerment-based intervention significantly improves the psychosocial aspects of diabetes and quality of life also in patients in active and effective self-care. Repeated educational interventions are the way towards a normal life with Type 1 DM.

A physical activity program to reinforce weight maintenance following a behavior program in overweight/obese subjects.

OBJECTIVE: To investigate the effects of a specific program to implement physical activity (fitness program) on weight loss maintenance, activity level and resting energy expenditure (REE). DESIGN: Observational study of subjects completing a behavioral program. SUBJECTS: In total, 200 overweight/obese subjects (36 males, aged 20-66 years; average BMI, 35.2 kg/m2). Program and measurements:The fitness program consisted of 12 bimonthly sessions, chaired by doctors and dietitians, involving groups of 8-12 subjects. Patients entered the program approximately 9 months after the end of behavioral treatment, during a weight loss maintenance period. The goal was set at a light-to-moderate daily physical activity (brisk walking), quantitatively measured by a pedometer; REE was measured before and after the fitness program by indirect calorimetry in a subset of patients. RESULTS: The fitness program restarted the process of weight loss in over 60% of subjects. At the end of the study, 84% of patients walked at least 5000 steps per day, compared with 24% at the beginning of the study. The probability of losing from 5 to 10% of initial body weight increased by 20% for any 1000 steps/day (OR, 1.20; 95% CI (confidence interval), 1.07-1.35), and that of losing more than 10% by over 30% (OR, 1.33; 95% CI, 1.19-1.49). REE increased significantly by 100 kcal/day (+7.5%), in spite of further weight loss (-1.8%). CONCLUSION: A specific fitness program in the weight maintenance phase after a behavioral program may significantly improve the long-term control of obesity.

Continuous care in the treatment of obesity: an observational multicentre study.

OBJECTIVES: To investigate weight loss and reasons for attrition in obese patients on long-term continuous care. DESIGN: Observational study with 36 months of follow-up. Setting. Fifteen Italian obesity centres applying a continuous care model of medical treatment. SUBJECTS: One thousand treatment-seeking obese subjects (785 females, median age 45.1 years, median BMI 37.4 kg m(-2)). Weight loss expectations were systematically recorded at baseline. INTERVENTIONS: An initial intensive treatment period (3-6 months) was followed by a less intensive continuous care (a follow-up control every 2-4 months). Main outcome measures. Attrition, reasons for treatment interruption and BMI change. Data were recorded by telephone interview in dropouts. RESULTS: Only 157 patients (15.7%) were in continuous treatment at 36 months. The main reasons of attrition were logistics, unsatisfactory results and lack of motivation. The only basal predictor for continuous care was lower Expected One-Year BMI Loss (P = 0.016). The probability of dropout increased systematically for any 5% expected BMI loss (Hazard ratio, 1.05; 96% confidence interval, 1.01-1.09). The mean percentage weight loss was greater in continuers (5.2% vs. 3.0% in dropouts; P = 0.016). However, the dropouts satisfied with the results or confident to lose additional weight without professional help reported a mean weight loss of 9.6% and 6.5% respectively. DISCUSSION: Continuous care produces long-term weight loss only in a subgroup of obese patients seeking treatment in medical centres. The finding that subgroups of dropouts report long-term weight loss has implication for the treatment of obesity.

Eating behavior affects quality of life in type 2 diabetes mellitus.

We evaluated the prevalence of disordered eating behavior in 168 unselected outpatients with type 2 diabetes mellitus (T2DM) and the effects on the health related quality of life (HRQL). Subjects in generally good glycemic control, treated by diet or oral hypoglycemic agents (58% M; 63.8+/-SD 10.1 years; BMI, 29.7+/-5.9 kg/m2) completed self-administered questionnaires for HRQL (SF-36) and eating behavior [(Three-Factor Eating Questionnaire (TFEQ); Binge Eating Scale (BES)]. Data on HRQL were computed as effectsizes in comparison to population norm. The prevalence of altered TFEQ scales was not different between genders, and varied between 22.1% (disinhibition) and 41.4% (restriction), but only 6.7% had a positive BES score. Age (OR, 0.58 for decade; 95% CI, 0.39-0.87), duration of diabetes (OR, 1.33 for 5 years; 1.01-1.74) and BMI (OR, 1.11; 1.04-1.18) were predictive for the presence of disinhibition. BMI also predicted hunger (OR, 1.16; 1.08-1.25). SF36 domains were not different in relation to positive BES. Disinhibition at TFEQ was significantly associated with poor social functioning (p=0.018) and role-emotional (p=0.022), whereas hunger was associated with poor physical functioning (p=0.010), role-physical (p=0.0014), social functioning (p=0.015) and role-emotional (p=0.0001). Metabolic control, duration of diabetes, and the presence of complications were not associated with HRQL. A disordered eating behavior may be present in T2DM patients, and is associated with poor HRQL. This condition must be considered for an olistic approach to weight control.

Weight cycling in treatment-seeking obese persons: data from the QUOVADIS study.

OBJECTIVE: To determine parameters of weight history useful for the assessment of weight cycling and their association with psychological distress and binge eating. DESIGN: Cross-sectional. SUBJECTS: A total of 1889 treatment-seeking obese subjects, enrolled by 25 Italian centers (78% female subject), aged 20-65 y (median 45); 1691 reported previous efforts to lose weight (median age of first dieting, 30 y). MEASUREMENTS: The number of yearly attempts to lose weight, weight gain since age 20 y, cumulative weight loss and gain were checked by a predefined structured interview. Psychological distress was tested by means of Symptom Check-List 90 (SCL-90), Binge Eating Scale (BES) and Three Factor Eating Questionnaire (TFEQ). RESULTS: Differences in anthropometric, clinical and psychological parameters were observed in relation to previous attempts to lose weight. Patients in the upper quartile of parameters of weight history were considered weight cyclers. In multivariate logistic regression analysis, after correction for age, sex and BMI, a high BES score was the only factor systematically associated with a high frequency of dieting (OR, 1.70; 95% confidence interval, 1.22-2.36; P=0.022), with higher cumulative weight loss (1.42; 1.12-1.80; P=0.003) and cumulative weight gain (1.38; 1.06-1.79; P=0.017). However, the sensitivity, specificity and positive predictive value of a high BES score were very low to detect cyclers. Weight cycling did not carry a higher risk of complicating diseases. CONCLUSIONS: Weight cycling is associated with psychological distress, and binge eating independently increases the risk, but cannot be used to predict cycling. Also, obese patients who do not experience overeating as a loss of control discontinue treatment or regain weight following therapy.

WHO and ATPIII proposals for the definition of the metabolic syndrome in patients with Type 2 diabetes.

AIMS: Different criteria have been proposed by the World Health Organization (WHO) and by the Third Report of the National Cholesterol Education Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATPIII) for the diagnosis of the metabolic syndrome. Its identification is of particular importance for coronary risk assessment. METHODS: The prevalence of the metabolic syndrome was determined according to the two different proposals in 1569 consecutive subjects with Type 2 diabetes. RESULTS: By the WHO proposal, 81% of cases (95% confidence interval, 79-83) were labelled as metabolic syndrome. Microalbuminuria had the highest specificity (99%) and visceral obesity the highest sensitivity (93%). Seventy-eight per cent of patients (95% CI, 76-80) fulfilled the ATPIII criteria for metabolic syndrome, low HDL-cholesterol having the highest specificity (95%), elevated blood pressure having the highest sensitivity. According to both proposals, 1113 patients were positive; 183 were concordantly negative, indicative of a fairly good agreement (k statistics, 0.464). Subjects only positive for the WHO proposal were more frequently males, had a lower BMI and a higher arterial pressure. Only subjects identified by the ATPIII proposal had a significantly higher prevalence of previously detected coronary heart disease. CONCLUSIONS: Minimum criteria for the metabolic syndrome are met in most patients with Type 2 diabetes. Correct identification of the syndrome is important for an integrated approach to reduce the high costs and the associated disabilities. The ATPIII proposal more clearly identifies the burden of coronary heart disease associated with the metabolic syndrome.

Cognitive behavioural therapy for obesity: one-year follow-up in a clinical setting.

Cognitive behavioural therapy (CBT) is the most comprehensive means of medically treating obesity, but only few data have so far been published concerning its long-term effectiveness. We here report our experience of 1068 consecutive patients (868 females) treated with CBT at a university-based obesity centre. The patients were enrolled into three different programmes: a 14-week LEARN programme (672 patients), a 16-week MOB programme for the morbidly obese (259 patients), or a 20-week BINGE programme for subjects affected by binge eating (137 patients). Eighty-five percent of the subjects completed the weekly programmes. The percentage of patients attending the scheduled control visits during the 1-year follow-up gradually decreased, being very low in the BINGE group (10%). The percentage weight loss was an average of 6% during the weekly courses, being higher in the MOB programme; by the end of the weekly sessions, it exceeded 10% of initial body weight in 22% of cases and increased to 36% during the follow-up. The cumulative probability of follow-up was higher among the patients undergoing the MOB and LEARN programmes than among the BINGE patients (p < 0.0001), and decreased with the increasing severity of obesity. Female gender and a weight loss of > 10% i.b.w. increased compliance to follow-up. The study further demonstrates the difficulty of achieving compliance to chronic management of obesity and the critical role of binge eating disorder in the medium-term treatment of obesity. Strategies are needed to improve adherence to a follow-up protocol.

Low ghrelin concentrations in nonalcoholic fatty liver disease are related to insulin resistance.

Several physiological and pathophysiological conditions, including changes in body fat, food intake, and insulin resistance, are known to be associated with variations in plasma ghrelin concentrations. We tested the hypothesis that insulin resistance exerts a primary role by measuring ghrelin in 86 patients with nonalcoholic fatty liver disease (NAFLD), a condition in which insulin resistance is relatively independent of obesity. Compared with 40 matched healthy subjects, patients with NAFLD had similar glucose levels and higher plasma insulin and insulin resistance [homeostasis model assessment (HOMA)-R index] by over 60%. Ghrelin was reduced (mean +/- SD, 226 +/- 72 pmol/liter in NAFLD vs. 303 +/- 123 in controls; P < 0.0001). In relation to quartiles of body mass index, ghrelin progressively decreased in controls (P = 0.003), but not in patients (P = 0.926). In relation to quartiles of HOMA-R, ghrelin decreased in both groups, and significantly correlated with HOMA-R. After adjustment for age and sex, HOMA-R was the sole factor significantly associated with low ghrelin in the whole group (odds ratio, 5.79; 95% confidence interval, 2.62-12.81; P < 0.0001) and specifically in NAFLD (2.96; 1.12-7.79; P = 0.028). The study suggests that insulin resistance is a major factor controlling ghrelin levels in subjects with and without NAFLD.

Psychiatric distress and health-related quality of life in obesity.

UNLABELLED: Health-related quality of life (HRQL) is poor in obese patients and not necessarily related to the severity of disease. In a large proportion of patients psychopathological distress is also present and its role on poor HRQL has never been quantified. METHODS: In 207 patients entering a University-based weight-reducing programme (38 males, 169 females), a package of self-administered questionnaires was submitted to measure HRQL (Short-Form 36) and psychopathological distress [general: Symptom Check-List 90 (SCL-90); depression: Beck Depression Inventory (BDI); binge eating: Binge Eating Scale (BES)]. Several clinical and anthropometric data were also recorded. RESULTS: HRQL, both in its physical and mental component, was significantly reduced in obesity when related to Italian population norms. SCL-90 identified psychopathological distress in 53 patients (26%), the BDI was indicative of depression in 89 cases (43%), whereas high scores of the BES were measured in 88 cases. Logistic regression analysis identified psichopathological distress as the major factor associated with poor HRQL. CONCLUSIONS: Psychiatric disturbances significantly contribute to poorly perceived health status. Only a comprehensive treatment including a specific approach to psychiatric symptoms may be effective in improving the perceived health status of obese patients seeking treatment.

The QUOVADIS Study: features of obese Italian patients seeking treatment at specialist centers.

Obesity is a major risk factor for several chronic diseases, but the burden associated with it also extends to psychosocial areas and to perceived health status. In 1999 an observational study on health-related quality of life in obesity was planned. The study was entirely web-based. Case Report Forms and the individual items of 7 self-administered questionnaires were directly implemented on a general database via an extranet system from 25 Italian centers. By December 2001, after enrolment had stopped, the database included anthropometric, socioeconomic and clinical data of 1944 patients (78% females). Weight-cycling was reported in over 80% of cases, overeating in 60-65%, structured physical activity in only 13-15%. Several chronic illnesses were associated. Whereas the prevalence of diabetes and hypertension was related to the degree of obesity, hyperlipidemia and coronary heart disease did not increase further with increasing obesity. A disturbed psychological mood was twice more common in females. Concern for present health was the main reason for seeking treatment in both genders; concern for body appearance was more common in females. Male subjects were more frequently assigned to dietary counseling and physical exercise, whereas in females psychotherapy was more frequently considered. Various forms of behavioral approach were planned in approximately 50% of patients. Finally, very few patients were initially considered for pharmacological intervention or bariatric surgery. The study provides a comprehensive picture of Italian patients seeking treatment for obesity. Data on perceived health status, psychological well being, body image awareness, eating behavior disorders and psychopathological distress will provide clues to a comprehensive assessment of obesity, the effects of treatments and reasons for failure.

The burden of obesity on everyday life: a role for osteoarticular and respiratory diseases.

The burden of obesity on patients' everyday life is high; obese subjects perceive a poor Health-Related Quality of Life (HRQL) in both physical and mental dimensions. We aimed to identify the areas of everyday life limited by health status and factors mainly responsible for perceived problems. The Nottingham Health Profile questionnaire (NHP) was used in 274 obese subjects seeking treatment at a university-based obesity center. Values were compared with normative Italian data, corrected for age and sex. Anthropometric and clinical data were also recorded, and correlated with health status. All domains of NHP were significantly impaired in obesity, the effect size ranging from 0.14 (Emotional Reactions; p = 0.02) to 0.99 (Physical Mobility; p < 0.0001), and varying in relation to gender, age and obesity class. Female subjects reported a higher-than-expected prevalence of problems in most areas of daily life [from 20% (Paid Employment) to 44% (Jobs around the home), compared with 14-26% in controls]. Males reported a high prevalence of problems in Sex life (31%), Holidays (37%) and Hobbies (49%), compared with 14, 14, and 16% in controls, respectively. Logistic regression analysis identified osteoarticular pain (knee and hip pain) and respiratory diseases as major factors predicting a poor HRQL in its physical dimensions, or perceived problems in everyday life. The relative importance of knee pain was higher than that of hip pain. Osteoarticular and respiratory diseases are major determinants of poor HRQL in obesity. Prevention strategies and treatment of somatic diseases are mandatory for a comprehensive approach to obesity.

Effects of cognitive-behavioural therapy on health-related quality of life in obese subjects with and without binge eating disorder.

OBJECTIVE: To measure the effects of cognitive-behavioural therapy on health-related quality of life (HRQL) in obese patients, in relation to binge eating disorder. DESIGN: Longitudinal, clinical intervention study consisting of structured sessions of cognitive-behavioural therapy, preceded by sessions chaired by a psychologist in subjects with binge eating. SUBJECTS: Two groups of obese patients (92 treated by cognitive-behavioural therapy (77 females); 76 untreated controls (67 female), selected from the waiting list (control group)). Of 92 treated patients, 46 had a binge eating disorder at psychometric testing and structured clinical interview. MEASUREMENTS: Health-related quality of life by means of Short-Form 36 questionnaire at baseline and after 3-5 months. RESULTS: Cognitive-behavioural treatment produced an average weight loss of 9.4+/-7.5 kg, corresponding to a BMI reduction of 3.48+/-2.70 kg/m(2). No changes were observed in the control group. All scales of HRQL improved in treated subjects (by 5-19%). In obese subjects with binge eating weight loss was lower in comparison to non-bingers (7.7+/-8.1 vs 11.1+/-6.6; P=0.034). However, the improvement in HRQL was on average larger, and significantly so for Role Limitation-Physical (P=0.006), Role Limitation-Emotional (P=0.002), Vitality (P=0.003), Mental Health (P=0.032) and Social Functioning (P=0.034). Bodily Pain was the sole scale whose changes paralleled changes in body weight. CONCLUSIONS: The positive effects of cognitive-behavioural therapy, mainly in subjects with binge eating, largely outweigh the effects on body weight, resulting in a significant change in self-perceived health status.

Role of sibutramine in the treatment of obese Type 2 diabetic patients receiving sulphonylurea therapy.

AIMS: To investigate whether the satiety-inducing agent sibutramine affected body weight and associated anthropometry in overweight and obese (body mass index (BMI) > 27) Type 2 diabetic patients on sulphonylurea therapy. METHODS: A randomized, placebo-controlled trial was undertaken in 134 patients with stable metabolic control on chronic sulphonylurea therapy. Patients were placed on moderate caloric restriction and received treatment with either sibutramine (15 mg/day) or placebo for 6 months. RESULTS: Fifty-three of 69 sibutramine-treated and 57/65 placebo-treated patients completed the study. Both groups showed progressive weight loss. At the end of the trial weight loss was two times greater in the sibutramine group (mean +/- SEM; -4.5 +/- 0.5 kg) than placebo (-1.7 plus minus 0.5 kg, P < 0.001 vs. sibutramine). There was a trend for more patients to lose > 5% of initial body weight in the sibutramine group than placebo. BMI (P < 0.001) and waist circumference (P < 0.001) were also decreased to a greater extent by sibutramine. Mean reductions in HbA(1c) were commensurate with weight loss in both the sibutramine and placebo (- 0.78 +/- 0.17% and -0.73 +/- 0.23%; P = 0.84). Sibutramine was well tolerated with only two patients withdrawn due to potentially drug-related serious adverse events (palpitations). CONCLUSIONS: Sibutramine, in conjunction with moderate caloric restriction, enhances weight loss and reduces waist circumference in overweight and obese Type 2 diabetic patients receiving sulphonylurea therapy. This is associated with additional improvements in glycaemic control in a limited number of patients losing > or = 10% of their baseline body weight.

WHO and ADA criteria for the diagnosis of diabetes mellitus in relation to body mass index. Insulin sensitivity and secretion in resulting subcategories of glucose tolerance.

OBJECTIVE: To determine the influence of body mass index (BMI) on agreement between the American Diabetes Association (ADA) and the new World Health Organization diagnostic criteria for the diagnosis of diabetes mellitus and to investigate the metabolic profile of the resulting subcategories. DESIGN: Cross-sectional study SUBJECTS: A total of 3018 subjects with no previous history of diabetes and fasting glucose <7.8 mmol/l, with a wide range of BMIs. MEASUREMENTS: (1) Prevalence of impaired glucose regulation (IGR) and diabetes (DM) according to ADA and WHO diagnostic criteria; (2) basal and post-load insulin sensitivity and secretion, calculated on the basis of data derived from an oral glucose tolerance test (OGTT). RESULTS: The diagnosis according to the two classifications was concordant in 2490 subjects, discordant in 528 (452 were identified as impaired glucose tolerance (IGT) and 76 as DM only by means of OGTT). The disagreement increased with increasing BMI, being as high as 25.3% in subjects with BMI > or = 35 kg/m(2). Subjects with isolated fasting hyperglycaemia were mainly characterised by reduced insulin sensitivity and secretion in the basal state, but normal first-phase insulin secretion and moderately reduced insulin sensitivity after glucose challenge. Subjects with isolated 2 h hyperglycaemia were mainly characterised by normal basal insulin secretion and by a marked insulin resistance associated with a blunted first-phase insulin secretion after the glucose load. CONCLUSIONS: The disagreement between ADA and WHO classifications is particularly relevant in obesity, making OGTT mandatory in these subjects. Different pathogenic mechanisms are involved in isolated fasting or post-load hyperglycaemia, possibly related to a different site of insulin resistance (hepatic vs peripheral), and/or to a different disregulation of insulin secretion (basal vs post-load). A correct identification of the underlying mechanism(s) is the rationale for future studies to detect the effectiveness of different pharmacological or behavioural approaches.

Metformin in non-alcoholic steatohepatitis.

There is no established treatment for steatohepatitis in patients who are not alcoholics. This disease is a potentially progressive liver disease associated with hepatic insulin resistance. Only a weight-reducing diet in overweight patients has proved effective. We treated 20 patients who had steatohepatitis but were not alcoholics with metformin (500 mg three times a day for 4 months), an agent that improves hepatic insulin sensitivity. When compared with the six individuals not complying with treatment, long-term metformin significantly reduced mean transaminase concentrations, which returned to normal in 50% of actively-treated patients. Also, insulin sensitivity improved significantly and liver volume decreased by 20%. Similar data have been reported in insulin-resistant ob/ob mice with fatty liver. A randomised-controlled study is needed.

Nonalcoholic fatty liver disease: a feature of the metabolic syndrome.

Insulin sensitivity (euglycemic clamp, insulin infusion rate: 40 mU. m(-2). min(-1)) was studied in 30 subjects with biopsy-proven nonalcoholic fatty liver disease (NAFLD), normal glucose tolerance, and a BMI <30 kg/m(2). Of those 30 subjects, 9 had pure fatty liver and 21 had evidence of steatohepatitis. In addition, 10 patients with type 2 diabetes under good metabolic control and 10 healthy subjects were studied. Most NAFLD patients had central fat accumulation, increased triglycerides and uric acid, and low HDL cholesterol, irrespective of BMI. Glucose disposal during the clamp was reduced by nearly 50% in NAFLD patients, as well as in patients with normal body weight, to an extent similar to that of the type 2 diabetic patients. Basal free fatty acids were increased, whereas insulin-mediated suppression of lipolysis was less effective (-69% in NAFLD vs. -84% in control subjects; P = 0.003). Postabsorptive hepatic glucose production (HGP), measured by [6,6-(2)H(2)]glucose, was normal. In response to insulin infusion, HGP decreased by only 63% of basal in NAFLD vs. 84% in control subjects (P = 0.002). Compared with type 2 diabetic patients, NAFLD patients were characterized by lower basal HGP, but with similarly reduced insulin-mediated suppression of HGP. There was laboratory evidence of iron overload in many NAFLD patients, but clinical, histological, and biochemical data (including insulin sensitivity) were not correlated with iron status. Four subjects were heterozygous for mutation His63Asp of the HFE gene of familiar hemochromatosis. We concluded that NAFLD, in the presence of normoglycemia and normal or moderately increased body weight, is characterized by clinical and laboratory data similar to those found in diabetes and obesity. NAFLD may be considered an additional feature of the metabolic syndrome, with specific hepatic insulin resistance.

Systemic prostaglandin E1 infusion and hepatic aminonitrogen to urea nitrogen conversion in patients with type 2 diabetes in poor metabolic control.

Amino acid catabolism and urea synthesis are increased in type 2 diabetes mellitus in poor metabolic control. In different catabolic conditions, prostaglandins (PGs) of the E series produced metabolic effects on nitrogen metabolism, decreasing urea formation. In 10 patients with type 2 diabetes in poor metabolic control, urea synthesis and amino acid to urea nitrogen exchange were measured in the basal state and during an alanine load (6 hours) with 2-hour superinfusion of a PGE1 analog (30 microg/h) or saline in random order. The urea synthesis rate was calculated as the sum of urinary urea excretion and urea accumulation in total body water (TBW); total nitrogen exchange was calculated as the difference between infused amino acid-nitrogen and urea appearance. Plasma alpha-aminonitrogen (alpha-amino-N) increased 100% in response to alanine, to a steady-state without differences in relation to PG superinfusion. The urea synthesis rate (mean +/- SD) was 34.0 +/- 11.4 mmol/h in the basal period and increased to 161.2 +/- 37.0 during alanine + saline and to 113.5 +/- 34.6 during alanine + PG (P < .001). Nitrogen exchange was negative at baseline (-25.0 +/- 9.0 mmol/h). It became moderately positive during alanine + saline (14.6 +/- 25.1) and far more positive during alanine + PG (53.5 +/- 21.4), with the difference due to reduced urea formation. The metabolic effects of PG were not related to differences in insulin and glucagon. We conclude that PGE1 slows the high rate of hepatic urea-N synthesis in poorly controlled type 2 diabetes. Such metabolic effects have therapeutic implications.